Ablative, renewable, multi-functional protective coating for dental surfaces

ABSTRACT

An oral care composition in the form of a toothpaste, tooth gel, dentifrice, tooth powder, prophy paste, mouthwash, rinse, tooth mousse, dental floss, chewing gum, soluble oral care strip or film for direct application or attachment to an oral surface, or lozenge for combating dental caries, erosion, hypersensitivity, and/or staining that includes an orally acceptable carrier and a copolymer of a first α, β-ethylenically unsaturated phosphate compound (A); and one or more α, β-ethylenically unsaturated co-monomers, at least one of which is other than an allyl-functional co-monomer, wherein (A) is an allyl phosphate compound of formula (A):
 
[CH 2 ═CH—CH 2 —O(R 1 O) a (R 2 O) b ] x P(O)(OM) 3-x   (A)
 
wherein, R 1  is a substituted or unsubstituted (C 2 -C 4 ) alkylene moiety; R 2  is a substituted or unsubstituted (C 2 -C 4 ) alkylene moiety; M is identical or different, hydrogen, alkali metal, ammonium, protonated alkyl amine, protonated alkanolamine, or protonated basic amino acid; X is 1 or 2, a is from 1 to 20; and b is from 0 to 20. Methods for combating dental caries, erosion, hypersensitivity, and/or staining are also provided.

RELATED APPLICATION AND CLAIM OF PRIORITY

This application is a divisional of U.S. patent application Ser. No.14/940,804, filed Nov. 13, 2015, which claims priority to U.S.Provisional Patent Application Nos. 62/078,996 and 62/079,001, bothfiled on Nov. 13, 2014. The disclosures of all of these applications areincorporated into this document by reference in their entireties.

BACKGROUND

Teeth are subject to various diseases and problems, among which arecaries, plaque, tartar, gingivitis, abusive whitening practices from useof concentrated hydrogen peroxide, hypersensitivity, and enamelstaining.

Most oral care diseases originate with the thin proteinaceous filmdeposited as pellicle onto tooth surfaces. This serves as a substratefor bacteria and mineral deposits which harden into plaque andeventually tartar. The bacterial colonies sheltered therein absorb andmetabolize nutrients from substances that pass through the oral cavity,particularly sucrose, and produce carboxylic acids. These acids are notreadily rinsed away by the oral fluids because the colonies areprotected and held in close proximity to the tooth surfaces by theplaque film. The acids produced, then, are held against the dentalsurfaces, where they slowly demineralize and destroy the hydroxyapatitecrystal structure, producing caries. The calculus and tartar depositscause separation of the gingival tissue from the tooth, causinginflammation and creating “pockets” which also provide a more sheltered,difficult to clean area for the destructive process. The recedinggingiva eventually expose the dentinal tubules, which results inhypersensitivity.

Other, more esthetic problems are halitosis and tooth staining. Theformer is assuaged by treatment with flavorants, mouth fresheners andanti-bacterial agents in the toothpaste or mouthwash formulation.Anti-bacterial agents, such as triclosan and cetylpyridinium chloride,also kill cariogenic bacteria, hence serve an anti-caries function aswell.

Separately, cetylpyridinium chloride, along with tea, coffee, wine,cigarette smoke and other factors may contribute to tooth staining. Thepopular methods of removing the stains are use of a more abrasivetoothpaste formulation and/or a “whitening agent”, commonly hydrogenperoxide. The concentration of the peroxide is steadily increasing inresponse to consumers' desire for more rapid and complete stain anddiscoloration removal. The problem associated with these treatments isthat the more abrasive toothpaste also wears down the tooth enamel andthe peroxide also oxidizes the amelogenin matrix that controls theorderly formation of the hydroxyapatite crystals in the naturalremineralization process. The more aggressive peroxide treatments havebeen associated with development of tooth hypersensitivity.

Simple organic phosphate ester surfactants have been shown to providenumerous oral care benefits, as described, for example, in U.S. Pat.Nos. 9,034,308 and 9,040,025 and references cited therein. Such estershave been shown to be effective cleaning agents for the removal ofdental surface residues and form protective films that inhibit theadherence of Streptococcus mutans to hydroxyapatite. Caries Res. 1991;25:51-57. Phosphate ester surfactants improve the efficacy of theanti-bacterial agents, such as triclosan, by enhancing its depositionand retention onto the tooth. U.S. Pat. Nos. 5,605,676, and 6,110,445.Similarly, phosphate ester surfactants have been claimed as an essentialingredient in a formulation with the milder carbamoyl peroxide as apotential replacement for hydrogen peroxide in toothpaste and mouthwashformulations. U.S. Publication No. 2009/0169493. The integrity of thephosphate ester surfactant films on hydroxyapatite was demonstrated bytheir ability to protect it from erosion by citric acid (fruit juices)and phosphoric acid (cola soft drinks). U.S. Publication Nos.2008/0247973 and 2010/0316579.

JP 2007/284609 describes copolymers based solely on phosphate esterfunctional (meth)acrylic ester monomers, Monomer A (e.g. the phosphateester of 2-hydroxyethyl methacrylate), the comonomers being selectedfrom a wide variety of non-phosphate functional monomers, “B”, “C” and“D”, as being useful for stain prevention and inhibition of bacterial orproteinaceous film deposition onto the tooth surface.

Although the overall effectiveness of the phosphate ester surfactants tominimize or eliminate the above problems is good, the duration of theprotection is limited by the structure. Both the monoalkyl and dialkylphosphate esters have only a single phosphate ester moiety to serve asthe point of attachment to the dental surface. The oral phosphataseenzymes can penetrate the surfactant film to eventually hydrolyze thephosphate ester link and destroy the film over a period estimated to beabout six to eight hours. To be more in line with personal oral hygienepractices of once daily tooth brushing, it would be desirable to atleast double this period of effectiveness and further improve the filmintegrity, durability and resistance to penetration.

SUMMARY

The present disclosure provides an oral care composition in the form ofa toothpaste, tooth gel, dentifrice, tooth powder, prophy paste,mouthwash, rinse, tooth mousse, dental floss, chewing gum, soluble oralcare strip or film for direct application or attachment to an oralsurface, or lozenge for combating dental caries, erosion,hypersensitivity, and/or staining that includes an orally acceptablecarrier and a copolymer of a first α, β-ethylenically unsaturatedphosphate compound (A); and one or more α, β-ethylenically unsaturatedco-monomers, at least one of which is other than an allyl-functionalco-monomer, wherein (A) is an allyl phosphate compound of formula (A):[CH₂═CH—CH₂—O(R¹O)_(a)(R²O)_(b)]_(x)P(O)(OM)_(3-x)  (A)

wherein, R¹ is a substituted or unsubstituted (C₂-C₄) alkylene moiety;R² is a substituted or unsubstituted (C₂-C₄) alkylene moiety; M isidentical or different, hydrogen, alkali metal, ammonium, protonatedalkyl amine, protonated alkanolamine, or protonated basic amino acid; Xis 1 or 2, a is from 1 to 20; and b is from 0 to 20.

Also described is an α, β-ethylenically unsaturated maleimide phosphatecompound of the formula (B):

wherein: R¹ is a substituted or unsubstituted (C₂-C₄) alkylene moiety;R² is a substituted or unsubstituted (C₂-C₄) alkylene moiety; M isidentical or different, hydrogen, alkali metal, ammonium, protonatedalkyl amine, protonated alkanolamine, or protonated basic amino acid; Xis 1 or 2, a is from 1 to 20; and b is from 0 to 20.

Oral care compositions incorporating the copolymers of the presentdisclosure and methods for combating dental caries, erosion,hypersensitivity, and/or staining by contacting a dental surface with anoral care composition are also disclosed.

DETAILED DESCRIPTION

While specific embodiments are discussed, the specification isillustrative only and not restrictive. Many variations of thisdisclosure will become apparent to those skilled in the art upon reviewof this specification.

As used herein, and unless otherwise indicated, the term “about” or“approximately” means an acceptable error for a particular value asdetermined by one of ordinary skill in the art, which depends in part onhow the value is measured or determined. In certain embodiments, theterm “about” or “approximately” means within 1, 2, 3, or 4 standarddeviations. In certain embodiments, the term “about” or “approximately”means within 50%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%,0.5%, or 0.05% of a given value or range.

In general, compositions according to the present disclosure includeoral care compositions in the form of a toothpaste, tooth gel,dentifrice, tooth powder, prophy paste, mouthwash, rinse, tooth mousse,dental floss, chewing gum, soluble oral care strip or film for directapplication or attachment to an oral surface, or lozenge for combatingdental caries, erosion, hypersensitivity, and/or staining that includean orally acceptable carrier and a copolymer, the copolymer being of afirst α, β-ethylenically unsaturated phosphate compound (A); and one ormore α, β-ethylenically unsaturated co-monomers, at least one of whichis other than an allyl-functional co-monomer, wherein (A) is an allylphosphate compound of formula (A)[CH₂═CH—CH₂—O(R¹O)_(a)(R²O)_(b)]_(x)P(O)(OM)_(3-x)  (A)whereinR¹ is a substituted or unsubstituted (C₂-C₄) alkylene moiety;R² is a substituted or unsubstituted (C₂-C₄) alkylene moiety;M is identical or different, hydrogen, alkali metal, ammonium,protonated alkyl amine, protonated alkanolamine, or protonated basicamino acid;X is 1 or 2,a is from 1 to 20; andb is from 0 to 20.

In some embodiments, the copolymer has a molecular weight andfunctionality selected so that the copolymer forms a film which protectsa dental surface from attachment of bacteria, plaque, and stainingagents while enhancing the deposition and retention of fluoride,anti-bacterial agents and/or gentle tooth whiteners onto the dentalsurface.

In some embodiments the one or more instances of R¹ and/or R² in thecompound of formula (A) are substituted with a hydroxy, alkoxy oraryloxy moiety.

In some embodiments, one or more instances of the (C₂-C₄) alkylenemoiety in formula (A) is substituted with a hydroxy, alkoxy or aryloxymoiety.

The first α, β-ethylenically unsaturated phosphate compound (allylphosphate compound) of formula (A) can be prepared by known methods. Forexample, U.S. Pat. No. 8,653,181, incorporated herein by reference inits entirety, describes methods for preparing allyl ethoxylate phosphateester embodiments of formula (A).

The α, β-ethylenically unsaturated co-monomers may be any such compoundbut preferably monomers that copolymerize well with allyl monomers andmay include those different from monomer (A) but still contain phosphateor other functional groups, such as carboxylate, or sulfonate. In someembodiments, one or more of the α, β-ethylenically unsaturatedco-monomers is an allyl functional sulfonate monomer such as, forexample, sodium 1-allyloxy-2-hydroxypropyl sulfonate or a non-allylmonomer, sodium 2-acrylamido-2-methylpropane sulfonate, sodium vinylsulfonate, sodium styrene sulfonate, acrylic acid or methacrylic acid,maleic acid, maleic anhydride (optionally, as its anhydride that ishydrolyzed post-polymerization), fumaric acid, itaconic acid and theirwater soluble salts, particularly their alkali metal or ammonium salts,as described in U.S. Pat. No. 9,115,236, incorporated herein byreference. In some embodiments, one or more of the α, β-ethylenicallyunsaturated co-monomers is an allyl ethoxylate or methallyl ethoxylate.In some embodiments, one or more of the α, β-ethylenically unsaturatedco-monomers is a compound according to formula (B), which is describedbelow. In some embodiments, one or more of the α, β-ethylenicallyunsaturated co-monomers is selected from combinations of any of theabove-mentioned co-monomers.

Although the acidic, ionic monomers may be copolymerized in either theacid or salt form, it is understood that it would be necessary to adjustthe pH of the final copolymer to physiological pH, hence at leastpartially converting the acidic groups to the salt forms.

Co-monomers are preferably selected and the polymerization processchosen to maximize incorporation of the monomers into the copolymeraccording to the desired distribution: random, alternating or in blocks.Preferably, the “-mer” units are distributed as evenly as possible alongthe polymer chain.

In some embodiments the first α, β-ethylenically unsaturated phosphatecompound (A), is an allyl phosphate compound of formula (A-1) wherein nis 1 to 20 (preferably 3 to 4):

As mentioned above, in some embodiments, one or more of the α,β-ethylenically unsaturated co-monomers is an α, β-ethylenicallyunsaturated maleimide phosphate compound of the formula (B):

whereinR¹ is a substituted or unsubstituted (C₂-C₄) alkylene moiety;R² is a substituted or unsubstituted (C₂-C₄) alkylene moiety;M is identical or different, hydrogen, alkali metal, ammonium,protonated alkyl amine, protonated alkanolamine, or protonated basicamino acid;X is 1 or 2,a is from 1 to 20; andb is from 0 to 20.

In some embodiments the one or more instances of R¹ and/or R² in thecompound of formula (B) are substituted with a hydroxy, alkoxy oraryloxy moiety.

In some embodiments, non-ionic monomers are used to balance thereactivities of the selected monomer mixtures and influence bulkproperties of the copolymer, such as water solubility, T_(g), toughness,durability or cost. These would include vinyl acetate, acrylate esters,methacrylate esters, maleate esters and diesters, fumarate diesters andstyrene.

In some embodiments, at least one of the co-monomers is a non-ionicmaleimidoalkoxylate co-monomer compound of formula (C):

whereinR¹ is a substituted or unsubstituted (C₂-C₄) alkylene moiety;R² is a substituted or unsubstituted (C₂-C₄) alkylene moiety;a is from 1 to 20; andb is from 0 to 20.

In some embodiments one or more instances of the (C₂-C₄) alkylene moietyis substituted with a hydroxy, alkoxy or aryloxy moiety.

An example of a suitable non-ionic maleimide alkoxylate comonomercompound is of the formula (C-1):

The maleimide derivatives may be prepared by reacting the proper primaryamine with maleic anhydride as reported in U.S. Pat. No. 5,306,828. Themonomer (C-1) can be set aside from the bulk of the maleimide for lateruse or a portion of the total charge could be phosphated with a reducedphosphation reagent charge, leaving excess (C-1) in the phosphateproduct mixture as a “non-ionic” monomer of similar polymerizationreactivity and a terminal hydroxyl group compatible with the othercomonomers. It would serve as a “diluent” monomer that could reduce thephosphate monomer content in the copolymer if that were desired.

Copolymers and terpolymers of additional ethylenically unsaturatedmonomers and the allyl alkoxylate phosphate esters of formula (A) and/ormaleimide polyalkoxylate phosphate esters of formula (B) can be preparedby synthesis methods described in U.S. Pat. No. 9,115,236.

Also presented is an α, β-ethylenically unsaturated maleimide phosphatecompound of the formula (B):

whereinR¹ is a substituted or unsubstituted (C₂-C₄) alkylene moiety;R² is a substituted or unsubstituted (C₂-C₄) alkylene moiety;M is identical or different, hydrogen, alkali metal, ammonium,protonated alkyl amine, protonated alkanolamine, or protonated basicamino acid;X is 1 or 2,a is from 1 to 20; andb is from 0 to 20.

In some embodiments the one or more instances of R¹ and/or R² in thecompound of formula (B) are substituted with a hydroxy, alkoxy oraryloxy moiety.

The α, β-ethylenically unsaturated maleimide phosphate compound offormula (B) can be prepared by several processes. In an embodiment,2-hydroxyethyl-2-oxyethyl amine (Diglycolamine, available from HuntsmanCorporation) is reacted with an approximately equimolar amount of maleicanhydride in chloroform according to an altered version of the methoddescribed in Example 1 of U.S. Pat. No. 2,980,652, with Diglycolaminesubstituted for the 1-(2-aminoethyl)imadazolidinone-2 used in theexample. The resultant compound is then ring closed according to analtered method of Example 5 of U.S. Pat. No. 2,980,652. In the alteredversion of the method, the resultant compound contains —CH₂CH₂OCH₂CH₂OHin place of the imidazolidinone-2 ring in the formula at lines 40-44 ofColumn 10 of the '652 patent. The resultant ring-closedhydroxy-functional maleimide compound is then phosphated by reacting itwith polyphosphoric acid and phosphoric anhydride according to analtered method of Example 1 of U.S. Pat. No. 5,550,274, with thehydroxy-functional maleimide compound substituted for the lauryl alcoholand adjusting the molar amount of the phosphation reagent to thespecific requirements of the process.

In some embodiments the maleimide phosphate compound of formula (B) is acompound of formula (B-1):

Also presented is a composition that includes a copolymer polymerizedfrom a monomer mixture comprising one or more α, β-ethylenicallyunsaturated maleimide phosphate compounds of formula (B) and one or moreα, β-ethylenically unsaturated co-monomers, at least one of which isother than maleimide-functional. In some embodiments, such compositionsare oral care compositions and further include an orally acceptablecarrier.

In some embodiments, one or more of the α, β-ethylenically unsaturatedco-monomers polymerized with one or more compounds of formula (B) is anallyl functional sulfonate monomer such as, for example, sodium1-allyloxy-2-hydroxypropyl sulfonate or a non-allyl monomer, sodium2-acrylamido-2-methylpropane sulfonate, sodium vinyl sulfonate, sodiumstyrene sulfonate, acrylic acid or methacrylic acid, maleic acid, maleicanhydride (optionally, as its anhydride that is hydrolyzedpost-polymerization), fumaric acid, itaconic acid and their watersoluble salts, particularly their alkali metal or ammonium salts, asdescribed in U.S. Pat. No. 9,115,236, incorporated herein by reference.In some embodiments, one or more of the α, β-ethylenically unsaturatedco-monomers is allyl ethoxylate (or polyethoxylate) or methallylethoxylate (or polyethoxylate). In some embodiments, one or more of theα, β-ethylenically unsaturated co-monomers is a compound according toformula (A), which is described above. In some embodiments, one or moreof the α, β-ethylenically unsaturated co-monomers is selected fromcombinations of any of the above-mentioned co-monomers.

In some embodiments, non-ionic monomers are used to balance thereactivities of the selected monomer mixtures and influence bulkproperties of the copolymer, such as water solubility, T_(g), toughness,durability or cost. These would include vinyl acetate, acrylate esters,methacrylate esters, maleate esters and diesters, fumarate diesters andstyrene.

Although the acidic, ionic monomers may be copolymerized in either theacid or salt form, it is understood that it would be necessary to adjustthe pH of the final copolymer to physiological pH, hence at leastpartially converting the acidic groups to the salt forms.

In some embodiments, the co-monomers are selected so that the copolymeris an alternating copolymer having essentially no homopolymerization. Insome embodiments, the co-monomers are selected so that the copolymer isan alternating copolymer exhibiting a degree of homopolymerization.

In some embodiments the α, β-ethylenically unsaturated phosphateco-monomer, is an allyl phosphate compound of formula (A-1):

wherein n is 1 to 20.

In some embodiments the α, β-ethylenically unsaturated phosphateco-monomer, is an allyl compound of formula (D-1):CH₂═CH—CH₂—O(CH₂CH₂O)_(a)—H  (D-1)wherein a is 1 to 20.

In some embodiments, one or more of the α, β-ethylenically unsaturatedco-monomers is one or more allyl functional monomers, which may behomologues of the polyalkylene oxide monoallyl ether starting materialsfor formula (A), formula (D):[CH₂═CH—CH₂—O(R₁O)_(a)(R₂O)_(b)]_(x)H  (D),wherein R₁, R₂, a, b, and X are defined as in formula (A).

In some embodiments, one or more of the α, β-ethylenically unsaturatedco-monomers is an allyl functional monomer of the formula (E):CH₂═C(R²)CH₂O(R³)(OH)SO₃M  (E)whereinR² is H or an alkyl radical;R³ is a linear or branched substituted or unsubstituted divalentaliphatic radical; andM is alkali metal, ammonium, protonated alkyl amine, protonatedalkanolamine, or protonated basic amino acid.

In some embodiments, one or more of the α, β-ethylenically unsaturatedco-monomers is selected from combinations of any of the above-mentionedco-monomers.

Also presented are oral care compositions that include one or more ofany of the phosphate copolymers according to the present disclosure.Compositions according to the present disclosure are suitable for use byhuman and nonhuman mammals. The term “oral care composition” as usedherein means a product that in the ordinary course of usage is retainedin the oral cavity for a time sufficient to contact some or all of thedental surfaces and/or oral tissues for purposes of oral activity. Theterm “dental surface” as used herein means a surface of a natural toothor a hard surface of artificial dentition including a denture, dentalplate, crown, cap, filing, bridge, dental implant, and the like.

In some embodiments, the oral care composition is selected fromtoothpastes, tooth gels, dentifrices, tooth powders, prophy pastes,mouthwashes, rinses, tooth mousse, dental floss, chewing gum, solubleoral care strips or films for direct application or attachment to oralsurfaces, or lozenges. In some embodiments, the oral care compositionincludes at least one copolymer having a molecular weight andfunctionality selected so that the copolymer forms a film that adheresto and protects a dental surface from acidic beverage or acid-refluxinduced erosion, hypersensitivity, attachment of bacteria, plaque, andstaining agents while enhancing the deposition and retention offluoride, anti-bacterial or gentle whitening agents onto the dentalsurface.

In some embodiments, the oral care composition includes an orallyacceptable carrier. In various embodiments, the carrier is a liquid,semi-solid or solid. A “liquid” can be a liquid of low or highviscosity. A liquid can be a liquid such that flow is imperceptibleunder ambient conditions. A liquid can be a thixotropic liquid. A“semi-solid” as used herein can be a gel, a colloid, or a gum. As usedherein, semi-solids and liquids are fluids distinguished on the basis ofviscosity: a semi-solid is a high viscosity fluid, while a liquid haslower viscosity. There is no definitive dividing line between these twotypes of fluids. A semi-solid can, in certain embodiments, have aviscosity as high as thousands of mPas. Carriers among those usefulherein include liquids, pastes, ointments, and gels, and can betransparent, translucent or opaque. In some embodiments, the orallyacceptable carrier includes water.

In some embodiments, the oral care composition includes an abrasivepolishing material. In some embodiments, the abrasive polishing materialis selected from silicas, aluminas, orthophosphates, polyphosphates,hexametaphosphates, and mixtures thereof. In some embodiments, the oralcare composition includes one or more additives. In some embodiments,the one or more additives are selected from polishing agents,anti-bacterial agents, foaming agents, binders, humectants, medicinalagents, sweetening agents, flavors, fluoride ion sources, peroxidesources, alkali metal bicarbonate salts, thickening materials, xylitol,sorbitol, coloring agents, sodium carbonate and mixtures thereof.

In some embodiments, the oral care composition includes a safe andeffective amount of a fluoride source. The fluoride source may besufficient to provide anticaries effectiveness. A wide variety offluoride ion-yielding materials can be employed as sources of solublefluoride in the present oral care compositions. Representative fluorideion sources include: sodium fluoride, potassium fluoride, sodiummonofluorophosphate, and combinations thereof.

In some embodiments, the oral care composition includes an abrasiveagent selected from one or more of hydrated silica, colloidal silica,fumed silica, insoluble sodium hexametaphosphate, insoluble sodiumaluminosilicates, sodium bicarbonate and mixtures thereof.

In some embodiments, one or more copolymers are present in a liquidcarrier.

In some embodiments, the oral care composition includes a phosphateester surfactant. Preferred phosphate ester surfactants include thosedescribed in U.S. Pat. No. 9,040,025, the disclosure of which isincorporated herein by reference in its entirety.

In some embodiments, the oral care composition is a tooth cleaningproduct, which includes one or more phosphate copolymers according tothe present disclosure, an abrasive agent, preferably free of calciumand other divalent ions, a surfactant, preferably a phosphate estersalt, and optionally a liquid.

Also provided are methods for combating dental caries, erosion,hypersensitivity, and/or staining. The method of use herein includescontacting a subject's dental surfaces and/or oral mucosa with the oralcare compositions according to the present disclosure. In someembodiments, the oral care composition is deposited as a protectivefilm. The method of treatment may be by brushing and/or rinsing. Othermethods include contacting the toothpaste, tooth gel, dentifrice, toothpowder, prophy paste, mouthwash, rinse, tooth mousse, dental floss,chewing gum, soluble oral care strips or films, or lozenges or otherform with the subject's dental surfaces and/or oral mucosa. Depending onthe embodiment, the oral care composition may be used as frequently as atoothpaste, or may be used less often, for example, weekly, or used by aprofessional in the form of a prophy paste or other intensive treatment.

It should be understood that any numerical range recited herein isintended to include all sub-ranges subsumed therein. For example, arange of “1 to 10” is intended to include all sub-ranges between andincluding the recited minimum value of 1 and the recited maximum valueof 10; that is, having a minimum value equal to or greater than 1 and amaximum value of equal to or less than 10. Because the disclosednumerical ranges are continuous, they include every value between theminimum and maximum values. Unless expressly indicated otherwise, thevarious numerical ranges specified in this application areapproximations.

The present disclosure will further be described by reference to thefollowing examples. The following examples are merely illustrative andare not intended to be limiting. Unless otherwise indicated, allpercentages are by weight of the total composition.

EXAMPLES Example 1. Synthesis of Terpolymer Based on Maleic Acid/Sodium1-Allyloxy-2-hydroxypropyl-3-sulfonate (SIPOMER COPS1)/Poly(oxyethylene) Allyl Ether Phosphate(alpha-2-Propen-1-yl-omega-hydroxypoly(oxy-1,2-ethanediyl) phosphate)(SIPOMER PAM 5000)

The following were introduced at room temperature, into a 1 literreactor, equipped with a mechanical stirrer and a condenser: 65.70 g ofa 40 wt. % aqueous maleic acid solution; 24.00 g of a 40 wt. % aqueoussolution of SIPOMER COPS 1 (SOLVAY monomer); 42.90 g of a 30 wt. %aqueous solution of SIPOMER PAM 5000 (SOLVAY monomer); and 213.00 gpurified water.

After deoxygenation with nitrogen bubbling for 30 minutes, the mixturewas brought to 80° C., with agitation. The following was then addedseparately, in one shot: 4.12 g of a 3 wt % aqueous solution ofmercaptoacetic acid, and 25.47 g of a 10 wt % aqueous solution of sodiumpersulfate. After 60 minutes reaction, 4.12 g of a 3 wt % aqueoussolution of mercaptoacetic acid was added in one shot. After another 60minutes reaction, 4.12 g of a 3 wt % aqueous solution of mercaptoaceticacid, and 25.47 g of a 10 wt % aqueous solution of sodium persulfatewere added separately, in one shot. The mixture was then held at 80° C.under agitation for 4 hours. After 6 hours total reaction time at 80°C., the mixture was cooled down to room temperature and transferred.

The number average molecular weight was 3900 g/mol. The theoreticaltotal solids was 12%.

Example 2

Following the procedure of Example 1, the quantities below of the samefour ingredients were combined in the stirred, deoxygenated solution andheated to 80° C.: 43.75 g of a 40 wt. % aqueous maleic acid solution;10.97 g of a 40 wt. % aqueous solution of SIPOMER COPS 1 (SOLVAYmonomer); 61.90 g of a 30 wt. % aqueous solution of SIPOMER PAM 5000(SOLVAY monomer); and 213.00 g purified water.

The mercaptoacetic acid and sodium persulfate aliquots were added asbefore, at the 1 and 2 hour mark after the first initiator/chaintransfer agent addition, the reaction was continued for four more hours,cooled and transferred. An alternative to mercaptoacetic acid is diethylphosphite HP(O)(OEt)₂.

The number average molecular weight was 3780 g/mol. The theoreticaltotal solids was 11.73%.

Example 3. Preparation of Copolymer Solutions

Test Solution 1 was prepared by dissolving 8.3 g of the copolymersolution from Example 1 in 91.7 g of water, to simulate a mouth rinse at1% by weight polymer. Test Solution 2 was prepared by dissolving 8.5 gof the copolymer solution from Example 2, in 91.5 g of water, tosimulate a mouth rinse at 1% by weight polymer.

Test Solution 3 was prepared by dissolving 10 g of Test Solution 2 in 90g of water, to create a solution at 0.1% by weight polymer with no addedsalt, i.e. 0 mol/L ionic strength. Test Solution 4 was prepared bydissolving 10 g of Test Solution 2 and 0.87 g of Sodium Chloride in89.13 g of water, to create a solution at 0.1% by weight polymer with0.150 mol/L NaCl ionic strength. Test Solution 5 was prepared bydissolving 10 g of Test Solution 2 and 1.72 g of Sodium Chloride in88.28 g of water, to create a solution at 0.1% by weight polymer with0.300 mol/L NaCl ionic strength.

Example 4. Adsorption of Polymers on Hydroxyapatite (HA) Surface

Adsorption on hydroxyapatite surfaces was analyzed as a mimic for teethand bone materials, of the same copolymer in different ionic strengthconditions, i.e. Test Solutions 3, 4 and 5 (cf. Example 3). The QuartzCrystal Microbalance with Dissipation Monitoring (i.e. QCM-D) techniquewas used to estimate the morphology (thickness, viscosity, andelasticity) of the physically adsorbed layer of the copolymer, firstin-situ (real time adsorption and desorption of copolymer in water) andafter drying. Test Solution 3 allowed determining these parameters inthe absence of added salt, while Test solutions 4 and 5 mimickeddifferent physiological conditions comparable to human saliva.

Description of the QCM-D technique can be found in Review of ScientificInstruments 64 (11): 3198-3205, 1993; in Review of ScientificInstruments 67 (9): 3238-3241, 1996 and in Physical Chemistry ChemicalPhysics 10 (31): 4516-34, 2008.

Test Procedure. Hydroxyapatite (HA) coated QCM sensors (referred to as“HA sensor” in the following) were supplied by Biolin Scientific(Cat/Model#QSX327; Hydroxyapatite sensors, 10 mm). All experiments werecarried out at physiological temperature of 37° C. For in-situ QCM-D, abaseline was first set using DI water (0 mM NaCl; pH 7) before the HAsensors were exposed, in separate experiments, to Test Solutions 3, 4 or5, for up to 15 min to reach a plateau of adsorption indicative of themaximum amount of polymer adsorbed. The flow rate of the test solutionsduring these in-situ experiments was set at 100 mL/min. Then the polymertreated HA sensors were exposed to deionized water (0 mM NaCl; pH 7) forup to 20 minutes of rinsing, to determine the resilience andremovability of the polymer layers deposited. For dry QCM-D, the rinsedsamples were dried in air and the areal mass of the deposited polymerwas measured in air at 37° C.

Results. In Table 1, in-situ polymer layer thicknesses before and afterrinsing with deionized water is provided, and in Table 2, the dry massdeposited as measured after the drying of the coated HA sensors isshown. In-situ and dry QCM results show that the polymer of TestSolution 3 in the lowest ionic strength condition (0 mM NaCl) alreadyadsorbs on HA surface, forming a 1 nm thick copolymer layer (cf.Table 1) and that after the rinsing and drying steps, the areal mass ofremaining polymer on hydroxyapatite still has a measurable value (196ng/cm2, cf. Table 2). The same polymer in higher ionic strengthconditions (i.e. Test Solutions 4 and 5, respectively 0.150 and 0.300mol/L NaCl) increasingly adsorbs on HA surface, forming thicker layers(respectively 3.2 and 5.2 nm, cf. Table 1), increasingly resists rinsing(respectively 2.5 and 3.8 nm, cf. Table 1) and show an increasing arealmass of remaining polymer on HA surface once dried, up to respectively291 and 421 nano grams/cm² (i.e. ng/cm²). The polymer of the testsolutions therefore reacts positively to higher ionic strength suitablefor human physiological conditions.

TABLE 1 QCM-D results of in-situ thickness of the adsorbed layer ofpolymer from Test Solutions 3, 4 and 5 (cf. Example 3), before and afterrinsing with deionized water. Test Solution 3 Test Solution 4 TestSolution 5 (0 mol/ (0.150 mol/ (0.300 mol/L L NaCl) L NaCl) NaCl) DuringDuring During expo- After expo- After expo- After sure rinsing surerinsing sure rinsing In situ 1.0 <1.0 3.2 2.5 5.2 3.8 thickness (nm)

TABLE 2 QCM-D results of dried polymer from Test Solutions 3, 4 and 5(cf. Example 3). Test Solution 5 Test Solution 3 Test Solution 4 (0.300mol/L (0 mol/L NaCl) (0.150 mol/L NaCl) NaCl) Dry mass 196 ± 16 291 ± 38421 ± 7 deposited (ng/cm²)

Example 5. In-Vitro Anti-Stain Testing of Copolymers on Bovine Teeth.Methods Adapted from Those in J. Dent. Res. 61(11):1236, 1982

Tooth Specimen Preparation. Bovine, permanent, central incisors were cutto obtain labial enamel specimens approximately 8×8 mm². The enamelspecimens were then embedded in an auto-polymerizing methacrylate resinso that only the enamel surfaces were exposed. The enamel surfaces werethen smoothed on a lapidary wheel and polished with flour of pumice andwater. They were then lightly etched to expedite stain accumulation andadherence. The specimens were then scored for pre-test color by means ofa Minolta C221, colorimeter, using the L, a* and b* values of the LABscale. The L a*b* scale is a way of measuring color. In this model, theL score, which is a light (score 100) to dark (score 0) measurement, ismost indicative of what one would see on teeth: the higher the L value,the lighter the color of a tooth; the smaller the L value, the morestained the tooth. All teeth had an initial L value around 70 to 80.Based on this score, the specimens were separated into groups of 12teeth, each group corresponding to the treatment they were going to beexposed to: water alone (reference mimicking no use of mouth rinse);test solution 1 of Example 1 or test solution 2 of Example 2.

Delta E=[(L−L_(o))²+(a*−a_(o)*)²+(b*−b_(o)*)²]^(1/2) is the overallchange of the color of a tooth, L a*b* being the color coordinated afterthe treatment and L_(o) a_(o)*b_(o)* those before. Delta L=L−L_(o),Delta a*=a*−a_(o)* and Delta b=b*−b_(o)* are the individual changes inthe color coordinates.

Test Procedure.

The specimens were immersed in pooled human saliva (room temp, slightstirring) for one hour to allow a pellicle film to form. Before thefirst exposure to a staining broth, they were allowed to sit for a fewminutes either in water, test solution 1 or test solution 2, mimickingexposure of teeth to a mouth rinse. They were then removed and allowedto dry for 15 seconds. They were placed in a staining apparatus,consisting of rods rotating and alternately immersing all the specimensin the staining medium or exposing them to air, mimicking the exposureto tea or coffee. Every hour, the specimens were removed from thestaining apparatus, patted dry with a towel and the appropriate testsolution was reapplied. After drying 15 seconds, the immersion cycleswere started up again. This would complete what is referred to as acycle: a.) exposure to a test solution, b.) alternate exposure tostaining broth or air for 1 hour and c.) drying. This continued for upto 4 cycles. At the end of the 4th staining cycle, the specimens wereplaced in the staining solution overnight on the staining apparatus. Thefollowing morning, the specimens were rinsed with water, lightly blottedand scored once again (L a*b*). This first day of treatment mimics afull day alternate exposure to a mouth rinse (or water as a reference)and to staining liquids, without ever brushing the teeth.

Results. The L a*b* color values developed in 4 staining cycles areshown in Table 3. The decrease in the L score of the teeth treated withtest solution 2 is smaller (−6.7) than that of the reference watersolution (−8.2), indicating that the reference was stained more heavilyand the polymer solution successfully retards staining and reduced thedarkening of the teeth by close to 20% in comparison to the control(water). Similarly, a* and b* scores increase less with test solution 2than they do with water, indicating less reddening and yellowing of theteeth. Finally, the overall color change Delta E is −1.9 points smallerwith test solution 2 than with water alone. In conclusion, all colormetrics after a 1-day stain accumulation were reduced by 20 to 30% withthe use of copolymer Test solution 2, versus the use of water.

TABLE 3 Reduction in 1-day Stain Accumulation onto Teeth by Applicationof Polymers. Number of cycles of N = 4 {test solution + staining}applications (1st day only) Color Coordinate Water Test Solution 2 %change Delta L −8.2 −6.7 −18% Delta a* 1.7 1.2 −29% Delta b* 5 3.8 −24%Delta E 9.8 7.9 −19%

Example 6. In-Vitro Stain Removal Testing of Copolymers on Bovine Teeth.Methods Adapted from Those in J. Dent. Res. 61(11):1236, 1982

Accentuated Staining Procedure. After the first day of staininginvolving 4 staining cycles and an additional overnight exposure tostaining broth (Example 4), the same staining procedure was repeated for4 additional days, 6 cycles per day, for a total of 28 staining cycleswithout ever brushing the teeth, to accentuate stain accumulation andtest the removal of tough stains. The final L a*b* color was recorded onthe 6th day after the last overnight immersion in a staining solution,rinsing and drying of the different specimens. Following this stainaccumulation, the specimens were brushed with a gentle, low abrasive,commercial dentifrice for 800 strokes (the normal PCR study amount) todetermine if the stains that had accumulated during 6 days had anydifferent removal characteristics. Following brushing, the specimenswere scored one final time. Percent (%) removal is defined as: %removal=(L_(after brushing)−L_(after staining))/(L_(after swung)−L_(initial))where L_(initial) is the initial L score of the tooth prior to anystaining, L_(after staining) is the final L score after the 28cycle-staining procedure and L_(after brushing) is the final score oncethe stained tooth has been brushed. Indeed,L_(after staining)−L_(initial) represents the amount of stain depositedover 28 cycles, while L_(after brushing)−L_(after staining) representsthe amount of stain successfully removed by brushing.

Results. The post brushing results are shown in Table 4. The specimenstreated with test Solutions 2 show 65% removal of 28-cycle stainaccumulation, in comparison to water (reference) which only allowsremoving 15% of the stain accumulated over the 5 days of stainingtreatment. Test Solution 1 removes even more, i.e. 76%, providingevidence for further improvement.

TABLE 4 Enhancement of Stain Removal by Pre-treatment of Teeth withCopolymer Solutions Followed by Brushing with Commercial Toothpaste. %Treatment removal Water −15% Test Solution 1 −76% Test Solution 2 −65%

In view of the above-described Examples, it is expected that daily useof copolymers of the present invention, alone or in combination withphosphate ester surfactants described in U.S. Pat. No. 9,034,308—in avariety of delivery vehicles, such as a toothpaste, tooth gel,dentifrice, tooth powder, prophy paste, mouthwash, rinse, tooth mousse,dental floss, chewing gum, soluble oral care strips or films, orlozenges—would provide a powerful, consumer friendly and easy to usearsenal to correct or prevent a wide range of common oral diseases inboth humans and other mammals.

The disclosed subject matter has been described with reference tospecific details of particular embodiments thereof. It is not intendedthat such details be regarded as limitations upon the scope of thedisclosed subject matter except insofar as and to the extent that theyare included in the accompanying claims.

Therefore, the exemplary embodiments described herein are well adaptedto attain the ends and advantages mentioned as well as those that areinherent therein. The particular embodiments disclosed above areillustrative only, as the exemplary embodiments described herein may bemodified and practiced in different but equivalent manners apparent tothose skilled in the art having the benefit of the teachings herein.Furthermore, no limitations are intended to the details of constructionor design herein shown, other than as described in the claims below. Itis therefore evident that the particular illustrative embodimentsdisclosed above may be altered, combined, or modified and all suchvariations are considered within the scope and spirit of the exemplaryembodiments described herein. The exemplary embodiments described hereinillustratively disclosed herein suitably may be practiced in the absenceof any element that is not specifically disclosed herein and/or anyoptional element disclosed herein.

While compositions and methods are described in terms of “comprising,”“containing,” or “including” various components or steps, thecompositions and methods can also “consist essentially of” or “consistof” the various components, substances and steps. As used herein theterm “consisting essentially of” shall be construed to mean includingthe listed components, substances or steps and such additionalcomponents, substances or steps which do not materially affect the basicand novel properties of the composition or method. In some embodiments,a composition in accordance with embodiments of the present disclosurethat “consists essentially of” the recited components or substances doesnot include any additional components or substances that alter the basicand novel properties of the composition. If there is any conflict in theusages of a word or term in this specification and one or more patent orother documents that may be incorporated herein by reference, thedefinitions that are consistent with this specification should beadopted.

We claim:
 1. An α, β-ethylenically unsaturated maleimide phosphatecompound of the formula (B):

wherein R¹ is a substituted or unsubstituted (C₂-C₄) alkylene moiety; R²is a substituted or unsubstituted (C₂-C₄) alkylene moiety; M isidentical or different, hydrogen, alkali metal, ammonium, protonatedalkyl amine, protonated alkanolamine, or protonated basic amino acid; Xis 1 or 2, a is from 1 to 20; and b is from 0 to
 20. 2. A compositioncomprising a copolymer polymerized from a monomer mixture comprising oneor more α, β-ethylenically unsaturated maleimide phosphate compounds ofclaim 1 and one or more other α, β-ethylenically unsaturated compounds,at least one of which is other than maleimide-functional.
 3. An oralcare composition in the form of a toothpaste, tooth gel, dentifrice,tooth powder, prophy paste, mouthwash, rinse, tooth mousse, dentalfloss, chewing gum, soluble oral care strip or film for directapplication or attachment to an oral surface, or lozenge for combatingdental caries, erosion, hypersensitivity, and/or staining comprising anorally acceptable carrier and a composition according to claim
 2. 4. Amethod for combating dental caries, erosion, hypersensitivity, and/orstaining comprising contacting a dental surface with the oral carecomposition of claim 3.